Exomic analysis of myxoid liposarcomas, synovial sarcomas, and osteosarcomas

Abstract

Bone and soft tissue sarcomas are a group of histologically heterogeneous and relatively uncommon tumors. To explore their genetic origins, we sequenced the exomes of 13 osteosarcomas, eight myxoid liposarcomas (MLPS), and seven synovial sarcomas (SYN). These tumors had few genetic alterations (median of 10.8). Nevertheless, clear examples of driver gene mutations were observed, including canonical mutations in TP53, PIK3CA, SETD2, AKT1, and subclonal mutation in FBXW7. Of particular interest were mutations in H3F3A, encoding the variant histone H3.3. Mutations in this gene have only been previously observed in gliomas. Loss of heterozygosity of exomic regions was extensive in osteosarcomas but rare in SYN and MLPS. These results provide intriguing nucleotide-level information on these relatively uncommon neoplasms and highlight pathways that help explain their pathogenesis.

Whole exome sequencing of a single osteosarcoma case¿integrative analysis with whole transcriptome RNA-seq data

“…The loss of heterozygosity has been reported to be extensive in OS exomes [39]. In the present case, we did not detect whole chromosome or gene region loss; however, we did detect the loss of heterozygosity in smaller regions.…”

“…We found no previous data about the associations between OS and these genes, except SBF1. With previous OS studies, another missense mutation (p.E1539K) has detected in SBF1 [39]. SBF1 is a SET (a nuclear oncogene) binding Table 7 The integrative analysis-genes with altered expression pattern [10] and SNVs annotated with ANNOVAR software Only the genes with lowest FDR value are presented.…”

Alternative lengthening of telomeres phenotype and loss of ATRX expression in sarcomas (Review)

“…These two domains have been reported to serve a role as chromatin remodelers (5). A third domain, predicted as a coiled coil structure, has been demonstrated to interact particularly with EZH2, a protein belonging to the polycomb multigenic family that is involved in histone methylation and deacetylation (6 identified in recent whole genome and/or whole exome genomic studies in sarcomas, particularly osteosarcoma (7)(8)(9)(10). Telomeres, the short, non-protein coding repeated hexameric TTAGGG sequences at each end of a chromosome, are involved in the control of genome integrity and chromosomal stability, and the development of cancer cells (11).…”

New Strategies in Sarcoma: Linking Genomic and Immunotherapy Approaches to Molecular Subtype

“…SNP analysis reveals more severe LOH in osteosarcoma than in myxoid liposarcoma or synovial sarcoma (14). In addition, osteosarcoma has one of the highest rates of structural variation of any pediatric cancer sequenced to date (12,15), with 50% to 85% of tumors exhibiting the hypermutation phenomenon termed kataegis (12,13).…”